The investigators propose to determine the complete genome sequence of Streptococcus mutans in this application. Decades of epidemiological, biochemical and animal studies have demonstrated that S. mutans is the principal causative agent of human dental caries (tooth decay). Dental caries is one of the most common infectious diseases afflicting humans, and in the United States, 84 percent of persons aged 17 years have evidence of present or past tooth decay. The cost of treating dental infections in the US is billions of dollars annually, and S. mutans is responsible for about 90 percent of these infections. Indeed, treatment of tooth decay caused by S. mutans accounts for about 50 percent of all US dental costs. Globally, the World Health Organization considers dental caries to be the most widespread oral disease in the world and reports that these infections are often untreated in many areas due to lack of available dental care. Additionally, S. mutans is occasionally associated with nonoral infections, principally subacute bacterial endocarditis. Considerable research effort and National Institute of Dental Research financial support has been expended in an effort to develop a vaccine to protect against S. mutans caused tooth decay, however, no truly effective strategy that prevents caries in humans has emerged. The principal investigator's laboratory was one of the first to investigate this organism at the molecular level and has been responsible for cloning, sequencing, and characterizing a number of genes including those encoding cell wall associated proteins, extracellular proteins involved with aggregation and production of adherent extracellular dextrans, and operons involved with the metabolism of sugars. Currently, the principal investigator's laboratory, in collaboration with Bruce A. Roe of the University of Oklahoma, Norman, is completing the sequence of the genome of Streptococcus pyogenes and assisting the laboratory of David W. Dyer of his department in the sequencing of the genome of Neisseria gonorrhoeae; both projects are funded by the NIH. The determination of the sequence of S. mutans will potentially lead to discovery of new and heretofore unknown genes and factors involved in virulence and pathogenicity, to new applications in molecular epidemiology and clinical diagnostics, to the elucidation of physiological factors essential for growth, and to rational approaches to new avenues to drug intervention and vaccine development.